Jing Pang1, Ju Cui1, Chao Xi2, Tao Shen1, Huan Gong1, Lin Dou1, Yajun Lin1, Tiemei Zhang1. 1. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China. 2. College of Life Sciences, Beijing Normal University, Beijing, China.
Abstract
BACKGROUND/AIMS: Excess energy intake leads to metabolic dysfunction, accompanied by oxidative stress and poly(ADP-ribose) polymerase (PARP) activation. METHODS: To determine the role of PARP activation in the incidence of metabolic dysfunction, PJ34, the PARP inhibitor, was administered to the oleic acid-treated hepatoma cells and high-fat diet-fed mice. The expression of genes was detected by quantitative real-time PCR and western blotting. Lipid droplets in the cells and tissues were stained with Oil Red O. RESULTS: PJ34 treatment aggravated oleic acid-induced lipid accumulation in hepatoma cells and induced SREBP1 expression by modulating the modification of transcription factor specificity protein 1 (Sp1). The high-fat diet-mice exhibited hyperglycemia, insulin resistance and lipid accumulation after 3 months of feeding. Although the serum level of lipid was not altered after PJ34 treatment, the expression level of lipogenic gene was up-regulated and the lipid accumulation was increased in the liver tissues of high-fat diet + PJ34-treated mice. In the high-fat diet + PJ34-treated mice, the insulin sensitivity was slightly changed and the levels of blood glucose and serum insulin were decreased compared with the mice fed with a high-fat diet alone. CONCLUSION: Taken together, PARP inhibition up-regulated the expression level of lipogenic gene and significantly induced lipid accumulation in the liver, which might worsen lipid metabolism disorders. These data will guide future research into the application of PARP inhibitors in the management of metabolic diseases.
BACKGROUND/AIMS: Excess energy intake leads to metabolic dysfunction, accompanied by oxidative stress and poly(ADP-ribose) polymerase (PARP) activation. METHODS: To determine the role of PARP activation in the incidence of metabolic dysfunction, PJ34, the PARP inhibitor, was administered to the oleic acid-treated hepatoma cells and high-fat diet-fed mice. The expression of genes was detected by quantitative real-time PCR and western blotting. Lipid droplets in the cells and tissues were stained with Oil Red O. RESULTS: PJ34 treatment aggravated oleic acid-induced lipid accumulation in hepatoma cells and induced SREBP1 expression by modulating the modification of transcription factor specificity protein 1 (Sp1). The high-fat diet-mice exhibited hyperglycemia, insulin resistance and lipid accumulation after 3 months of feeding. Although the serum level of lipid was not altered after PJ34 treatment, the expression level of lipogenic gene was up-regulated and the lipid accumulation was increased in the liver tissues of high-fat diet + PJ34-treated mice. In the high-fat diet + PJ34-treated mice, the insulin sensitivity was slightly changed and the levels of blood glucose and serum insulin were decreased compared with the mice fed with a high-fat diet alone. CONCLUSION: Taken together, PARP inhibition up-regulated the expression level of lipogenic gene and significantly induced lipid accumulation in the liver, which might worsen lipidmetabolism disorders. These data will guide future research into the application of PARP inhibitors in the management of metabolic diseases.
Authors: Anita K Mehta; Emily M Cheney; Christina A Hartl; Constantia Pantelidou; Madisson Oliwa; Jessica A Castrillon; Jia-Ren Lin; Katie E Hurst; Mateus de Oliveira Taveira; Nathan T Johnson; William M Oldham; Marian Kalocsay; Matthew J Berberich; Sarah A Boswell; Aditi Kothari; Shawn Johnson; Deborah A Dillon; Mikel Lipschitz; Scott Rodig; Sandro Santagata; Judy E Garber; Nadine Tung; José Yélamos; Jessica E Thaxton; Elizabeth A Mittendorf; Peter K Sorger; Geoffrey I Shapiro; Jennifer L Guerriero Journal: Nat Cancer Date: 2020-12-14
Authors: Anita K Mehta; Sapana Kadel; Madeline G Townsend; Madisson Oliwa; Jennifer L Guerriero Journal: Front Immunol Date: 2021-04-23 Impact factor: 7.561